System for controlling flow through a line during intravenous drug delivery

ABSTRACT

A system for controlling flow through a line during intravenous drug delivery. The system is capable of use in conjunction with a bedside-pharmacy system for the preparation and delivery of intravenous drugs. The system includes a disposable cassette with first and second valve chambers and a control unit into which the cassette is capable of being received. The control unit has a cam and first and second actuators. The bedside-pharmacy system may include a liquid inlet for connection to a liquid supply, vial receptacles, and a liquid outlet for providing the intravenous drug in mixed, liquid form to the patient. That system may include a chamber having a variable volume, and a valve mechanism, which may be actuated to control flow between the liquid outlet, the variable-volume chamber, the vial receptacles and the liquid inlet. That system induces change in the volume of the variable-volume chamber and actuates the valve mechanism, so as to introduce liquid from the liquid inlet into the vials and reconstitute or dilute the drugs and so as to deliver the drugs to the patient.

RELATED U.S. APPLICATION(S)

[0001] The present application is a divisional application of Ser. No.09/359,237, filed Jul. 22, 1999, which is a divisional application ofSer. No. 09/137,025, filed Aug. 20, 1998, which, in turn, is acontinuation-in-part of two U.S. patent applications filed Aug. 22,1997, the first having Ser. No. 08/916,890, now abandoned, and thesecond having Ser. No. 08/917,537, which issued as U.S. Pat. No.6,165,154 on Dec. 26, 2000. These applications are hereby incorporatedherein by reference.

TECHNICAL FIELD

[0002] The present invention relates to devices and methods for thepreparation and delivery of intravenous drugs.

SUMMARY OF THE INVENTION

[0003] The invention is directed to a system for controlling flowthrough an intravenous line. The system has a disposable cassettecapable of being received into a control unit. The disposable cassettepreferably has a first valve chamber defined by a first rigid wall and afirst flexible membrane, and a second valve chamber defined by a secondrigid wall and a second flexible membrane; and the control unitpreferably has a cam, a first actuator disposed adjacent the firstflexible membrane so that movement of the first actuator causes a changein pressure on the first flexible membrane, and a second actuatordisposed adjacent the second flexible membrane so that movement of thesecond actuator causes a change in pressure on the second flexiblemembrane, wherein the cam and actuators are disposed with respect toeach other such that, as the cam is rotated, the actuators are moved.The cam is preferably shaped so that at any time at least one actuatoris urging the corresponding flexible membrane into a closed position.The cassette may also include a pressure-conduction chamber located in afluid passageway between the first and second valve chambers.

BRIEF DESCRIPTION OF THE DRAWINGS

[0004]FIG. 1 is a perspective view of a system according to a preferredembodiment of the present invention.

[0005]FIG. 2 is a rear view of the cassette that may be used in thesystem of FIG. 1, along with three vials attached to the cassette.

[0006]FIG. 3 is a front view of a cassette that may be used in thesystem of FIG. 1.

[0007]FIG. 3A is a perspective view of the cassette of FIG. 3.

[0008]FIG. 4 is a schematic showing the fluid pathways through thecassette of FIG. 3.

[0009]FIG. 5 is a top view of the back-plate component of the cassetteof FIG. 3.

[0010]FIG. 6 is a front view of the back-plate component shown in FIG.5.

[0011]FIG. 7 is a left side view of a membrane used in thefree-flow-prevention valve of the cassette of FIG. 2.

[0012]FIG. 8 is a rear view of the membrane of FIG. 7.

[0013]FIG. 9 is a cross-sectional view of the membrane shown in FIGS. 7and 8 across lines 9-9.

[0014]FIG. 10 is a front view of the membrane of FIG. 7.

DETAILED DESCRIPTION OF SPECIFIC EMBODIMENT

[0015]FIG. 1 shows a system for the preparation and delivery of drugsaccording to a preferred embodiment of the invention. Powdered drugs areprovided in vials 11 and are mixed by the system with a liquid providedin container 13. The system includes a disposable cassette 17, which isdisposed of between patients, and a control unit 15, which receives andcontrols the cassette, and which is used over and over. In general,liquid flows from container 13, is directed by the cassette 17 to a vial11 so as to reconstitute the powdered drug or dilute a liquid drug toits proper concentration, and then is directed by the cassette to thepatient. During periods of the drug-delivery cycle, liquid fromcontainer 13 may be directed by cassette 17 directly to the patientwithout being mixed with a drug. Premixed drugs may be delivered by thesystem from the vials to the patient and from a bag connected to a luerport (item 26 in FIGS. 2 and 3) on the cassette. The specific embodimentdiscussed herein uses separate mixing and delivery chambers. It will beappreciated by one of ordinary skill in the art, that a singlevariable-volume chamber may be used to accomplish both mixing anddelivering.

[0016]FIG. 2 shows a rear view of a cassette 17 that may be used in thesystem of FIG. 1. (i.e., FIG. 2 shows the side of the cassette thatfaces away from the control unit 15.) FIG. 3 shows a front view (i.e.,the control-unit side) of a cassette 17, and FIG. 3A shows a perspectiveview of the cassette. Some of the features used in this cassette 17 arealso used in the cassette disclosed in above-referenced U.S. Pat. No.6,165,154 and its parent U.S. application, having Ser. No. 08/478,065filed Jun. 7, 1995, now U.S. Pat. No. 5,755,683, issued May 26, 1998.FIG. 2 shows three vials 11 a-11 c attached respectively to spikes 21a-21 c. Liquid entering the cassette 17 from container 13 (shown inFIG. 1) passes through port 22, and liquid going to the patient exitsthe cassette through port 23. An air vent 24 permits air to be drawninto the cassette to be directed into a vial to replace liquid leavingthe vial or to be directed through the cassette's passageways 25 inorder to remove any liquid in the passageways. A luer port 26 permits apremixed drug container or alternate diluent source to be attached tothe cassette. The cassette has two pressure-conduction chambers: adelivery chamber 27 and a mixing chamber 28, both of which are coveredby a flexible membrane.

[0017] Valves 31 a-31 i control flow through the passageways 25. Thesevalves 31 a-31 i are preferably membrane-covered valves of the typeshown in FIGS. 1 and 9 of U.S. Pat. No. 5,088,515. The membranes ofthese valves 31 a-31 i may be forced into a closed position by pressureexerted by the control unit. This pressure may be positive air pressureprovided by the control unit, or in one preferred embodiment, thepressure may be exerted by a mechanical actuator mounted in the controlunit.

[0018] Valves 31 b and 32 control flow into and out of delivery chamber27. In a preferred embodiment, these two valves 31 b and 32 are eachcontrolled by an actuator, and these two actuators are controlled by asingle cam. The cam and the actuators are arranged so that, at alltimes, at least one of valves 31 b and 32 is closed. In other words,sometimes both valves are closed, sometimes one valve is opened and theother is closed, but both valves are never opened at the same time. Suchan arrangement assures that liquid does not free flow through thedelivery chamber.

[0019] Valve 32 controls flow from the delivery chamber 27 to thepatient. Valve 32 is preferably of the type shown in FIGS. 18 and 19 ofU.S. Pat. No. 5,755,683. The membrane of valve 32 has a portion that,when actuated by the control unit, seals off the mouth located withinthe valving chamber (in the same manner as valves 31 a-31 i) and anotherportion that is more compliant. Valve 32 works in conjunction with thestopcock valve 33, so as to smooth out the delivery of fluid, in themanner described in U.S. Pat. No. 5,755,683. The control unit includes awheel or other mechanism for receiving and rotating the cassette'sstopcock valve 33.

[0020] Similar to the cassette described in U.S. Pat. No. 5,755,683, thebody of the cassette 17 shown in FIGS. 2 and 3 is preferably made fromthree thermoplastic layers ultrasonically welded together. Most of thepassageways 25 are formed between the back layer and the middle layerand are defined by the back and middle layers and channel walls 37. In apreferred embodiment, the channel walls 37 extend from the middle layerand are sealingly attached to the back layer by an ultrasonic weld. Someof the walls 29 between the back and middle layers do not definepassageways but merely provide structural rigidity. The front and middlelayers define several sections 38 of the fluid passageways, and thefront and middle layers hold the membranes for the delivery chamber 27,the mixing chamber 28 and the valves 31 a-31 i, 32. Walls 39 areprovided on the front side of the middle layer to permit easierultrasonic welding of the channel walls between the back and middlelayers.

[0021] Each of the vial spikes 21 a-21 c may be provided with a spikecap 21′ to keep the cassette and spikes safe and sterile during storageand handling. Similarly, the luer port 26 may be provided with a cap 26′to keep the cassette sterile.

[0022] The inlet port 22 and the outlet port 23 are respectivelyprovided with free-flow-prevention valves 34 and 35, which areautomatically closed by the control unit when the door holding thecassette is opened. These free-flow-prevention valves are discussed ingreater detail below in connection with FIGS. 7-10.

[0023]FIG. 4 is a schematic showing how the valves control the flow offluid through the cassette shown in FIGS. 2 and 3. In a typicalapplication, the inlet 22 of the cassette is attached to an IV solutionsource (item 13 in FIG. 1), the luer port is connected to a liquidmedicine supply, and each of the spikes (items 21 a-21 c in FIG. 3) maybe attached to a vial 11 a-11 c containing a powdered drug that must bereconstituted by the IV solution source or containing a liquid drug thatmay or may not need to be diluted before being delivered to the patient.

[0024] Dilution is performed by pulling liquid from the solution source(item 13 in FIG. 1) and the vial to the mixing chamber in theappropriate proportions. Of course, it is important that the drugs bediluted the correct amount so as to avoid sending to the patient a drugsolution that is too concentrated or too diluted. To ensure the correctamount of dilution, liquid from the IV solution source is measured inthe delivery chamber 27 before being sent to the mixing chamber.

[0025] An example of a typical drug-delivery cycle first prepares thedrug from vial 11 a for delivery to the patient, then the drug from vial11 b, then the drug from vial 11 c and then the liquid drug providedthrough the luer port 26. (Of course, variations of this drug-deliverycycle may be implemented.) To implement such a cycle, the control unit(item 15 of FIG. 1) actuates the membrane-based valves 31 a-31 i and 32,as well as the stopcock valve 33.

[0026] After the cassette has been primed, valves 31 a and 31 b areopened (with all the other membrane-based valves 31 c-31 i, 32 keptclosed), and the control unit applies a negative pressure for aspecified amount of time against the membrane of the delivery chamber27, so as to draw liquid from the IV solution source into the deliverychamber. In a preferred embodiment, the rigid wall defining thevariable-volume delivery chamber includes a bulge or other irregularityto make the membrane defining the delivery chamber less stable when thechamber is at its lowest volume; this instability makes it easier forthe membrane to be pulled away from the rigid portion.

[0027] After a sufficient amount of liquid has been introduced into thedelivery chamber 27, valve 31 a is closed, and the control unit uses,for example, the bubble-detection method taught in U.S. patentapplication Ser. No. 08/477,380 filed Jun. 7, 1995, now U.S. Pat. No.5,641,892, issued Jun. 24, 1997 (which is incorporated herein byreference) to determine whether there is any air in the delivery chamber27. If there is any air bubble in the delivery chamber 27, theapplication of pressure by the control unit against the deliverychamber's membrane may be used to force the air bubble to the IVsolution source (through port 22), the air vent 24 (if it is capable ofventing air in two directions) or the mixing chamber; to which of thesethree locations the bubble is directed depends on whether valve 31 a,valve 31 g or valve 31 h is opened by the control unit.

[0028] After any bubble has been eliminated from the delivery chamber27, the control unit takes a measurement of how much air is in the spacedefined by the control unit outside of and adjacent to the deliverychamber's membrane; in a preferred embodiment, the control unit uses anacoustic volume measurement system, such as that taught in U.S. Pat. No.5,349,852 (which is also incorporated herein by reference). If thecombined total volume of the delivery chamber and the space adjacentthereto is known, the amount of liquid in the delivery chamber may bedetermined by subtracting the measured volume of air from the knowntotal volume.

[0029] Before any drugs are mixed, it may be desired to deliver some IVsolution to the patient in order to establish flow through the line fromthe outlet 23 to the patient and through the patient's vein. In order todeliver liquid from the delivery chamber 27 to the patient, valve 32 isopened while the stopcock valve 33 is controlled and while pressure isapplied to the delivery chamber's membrane by the control unit. (Thevalve 32 and stopcock valve 33 may be controlled in the manner describedin U.S. Pat. No. 5,755,683 referenced hereinabove). The stopcock valveand pressure may be adjusted to control the rate of fluid delivered.

[0030] After an amount of fluid is delivered from the delivery chamber27 to the patient, the volume of liquid delivered to the patient may bedetermined by taking another measurement of the volume of air defined bythe control unit adjacent to and outside of the delivery chamber.Subtracting the volume of air measured before any liquid has beendelivered from the volume of air measured after the liquid has beendelivered provides the volume of liquid delivered to the patient. Byusing the acoustic volume measurement system of U.S. Pat. No. 5,349,852,and opening valve 32 and stopcock valve 33 at the same time the amountof liquid delivered may be tracked in real time as it is beingdelivered.

[0031] After the amount of liquid delivered from the delivery chamber 27has been determined, the delivery chamber may be refilled by closingvalve 32, as well as valves 31 c-31 i, and then opening valves 31 a and31 b. The control unit again applies a negative pressure against thedelivery chamber's membrane so as to draw liquid from the IV solutionsource into the delivery chamber 27. This additional IV solution mayalso be directed straight to the patient again in the manner describedhereinabove, or it may be used in the admixture process in the mixingchamber. In a preferred embodiment, the volume of liquid in the deliverychamber is split, with a portion being delivered to the patient and theremainder being sent to the mixing chamber, where the liquid is used toreconstitute the drugs in the vials.

[0032] In order to reconstitute a powdered drug, liquid is introducedinto the vial containing the powdered drug. With the cassette embodimentdepicted in FIGS. 2-4, a mixing chamber 28 separate from the deliverychamber 27 is used to mix the IV solution with the drug. As noted above,it will be appreciated that, in an alternative embodiment, a singlechamber may be used. In order to reconstitute the drug properly, it isimportant that the correct amount of IV solution be introduced into thevial. Typically, the correct volume of IV solution necessary toreconstitute the drug is more than the volume of the delivery chamber 27(which in a preferred embodiment is 4 ml).

[0033] There are two basic types of drug preparation cycles: those drugswhich come in powdered form requiring reconstitution, and those comingin liquid form which may or may not need dilution.

[0034] In a typical reconstitution cycle, IV solution is firstintroduced from the IV solution source into the delivery chamber 27. Thecontrol unit then determines whether there are any air bubbles in thedelivery chamber 27 and, if there is none, makes a measurement of thevolume of air defined by the control unit adjacent to and outside of thedelivery chamber. With valves 31 a-31 g, 31 i and 32 closed, and valves31 b and 31 h opened, IV solution is forced from the delivery chamber 27to the mixing chamber 28 by the control unit applying a positivepressure to the delivery chamber's membrane and/or a negative pressureto the mixing chamber's membrane. The volume of liquid delivered to themixing chamber may be determined by taking another measurement of thevolume of air defined by the control unit adjacent to and outside of thedelivery chamber. Subtracting the volume of air measured before anyliquid has been delivered to the mixing chamber 28 from the volume ofair measured after the liquid has been delivered to the mixing chamberprovides the volume of liquid delivered to the mixing chamber.

[0035] In order to introduce more IV solution into the mixing chamber,valve 31 h is closed again and valve 31 a opened to fill the deliverychamber 27 again with IV solution. Valve 31 a is closed, abubble-detection cycle is performed, and a measurement of the air volumeis again taken. Then valve 31 h is opened again, and IV solution isforced from the delivery chamber 27 to the mixing chamber 28. Anothermeasurement of the air volume is taken in order to determine the volumeof additional IV solution delivered to the mixing chamber. This cycle isrepeated as often as necessary to introduce the correct amount of IVsolution into the mixing chamber 28.

[0036] Once the mixing chamber 28 is filled with the desired amount ofIV solution, the process of reconstituting the powdered drug may begin.In order to reconstitute the drug in vial 11 a, valves 31 d and 31 i areopened, with all the other valves 31 a-31 c and 31 e-31 h kept closed.The control unit applies pressures to the membrane of the mixing chamber28 to force the IV solution therein into the vial 11 a.

[0037] Since the pressure within the vial often varies from the ambient(either being positively pressurized or having a partial vacuum), it isoften desirable to check the pressure within the vial before thereconstitution process begins. It may be difficult to generate enough ofa pressure differential between the mixing chamber 28 and the vial 11 ato create a sufficiently strong spray to reconstitute the powdered drug,if the vial is positively pressurized. Since, it is usually preferableto bring the vial down to ambient pressure before the reconstitutionprocess begins, it is preferred to check the vial pressure before themixing chamber 28 is filled with IV solution. In order to check whetherthe vial 11 a is positively pressurized, valves 31 d and 31 h areopened, with all the other valves 31 a-31 c, 31 e-g and 31 i keptclosed; the mixing chamber 28 is kept substantially empty. If the vial11 a is positively pressurized, air escapes from the vial 11 a into themixing chamber 28. The control unit preferable includes a pressuretransducer that measures the pressure of the mixing chamber 28 (as wellas a pressure transducer that measures the pressure of the deliverychamber 27). The control unit measures whether there is an increase inthe pressure of the mixing chamber 28; the presence and size of apressure increase indicates whether and how much the vial 11 a ispressurized. By applying a negative pressure against the mixingchamber's membrane additional air may be removed from the vial 11 a tothe mixing chamber 28, so as to bring the vial 11 a to ambient. Themixing chamber 28 may be able to hold the excess air from the vial 11 aalong with the amount of IV solution necessary to reconstitute the drugin the vial 11 a, or if there is too much excess air it may be forcedfrom the mixing chamber 28 through valve 31 i to the IV solution source(through port 22) or to the air vent 24 (if it is capable of venting airin two directions)—or even to another vial 11 b or 11 c if it hasalready been emptied.

[0038] If the vial 11 a has a partial vacuum, the partial vacuum doesnot of course interfere with the delivery of IV solution from the mixingchamber 28 to the vial 11 a. A partial vacuum may, however, interferewith the drawing of liquid from the vial back to the mix chamber. Inorder to eliminate a partial vacuum, air may be drawn from vent 24 intothe vial 11 a. One way to determine whether a partial vacuum exists invial 11 a is to fill the delivery chamber 27 with air (from the vent 24)and then, after valve 31 g to the vent 24 is closed, opening valve 31 dto permit fluid communication between the delivery chamber 27 and thevial 11 a. The pressure in the delivery chamber 27 drops if the vial 11a has a partial vacuum. It is preferred that the vial be tested firstfor positive pressurization before being tested for a partial vacuum, sothat if there is positive pressurization no powdered drug isaccidentally blown into the delivery chamber 27, but rather is blowninto the mixing chamber 28.

[0039] After the vial 11 a is brought to ambient pressure (if necessary)and after the mixing chamber 28 is filled with the desired amount of IVsolution, IV solution is sprayed into the vial 11 a by the applicationof pressure by the control unit onto the mixing chamber's membrane. Inorder to ensure that the powdered drug is sufficiently mixed with the IVsolution, the liquid is drawn back from the vial 11 a into the mixingchamber 28, and then in a preferred embodiment, resprayed into the vial11 a. This process is repeated several times. Quickly sloshing theliquid back and forth between the vial 11 a and the mixing chamber helpsensure that the powdered drug in vial 11 a is fully dissolved by the IVsolution.

[0040] Air pressure in the vial is managed during the repeated agitationto the mixing chamber by pulling and pushing air and fluid to and fromthe bottom and the top of the mixing chamber. Thus, flow into and out ofthe mixing chamber 28 is controlled by two valves, an upper valve 31 h,which permits air to leave the mixing chamber before liquid leaves themixing chamber, and a lower valve 31 i, which permits liquid to leavethe mixing chamber before air leaves the mixing chamber. The top port,shown in FIG. 2 as item 47, is used to introduce liquid into the mixingchamber and is used to remove air from the mixing chamber. The top portis shaped in accordance with the valve shown in FIGS. 22-24 of U.S. Pat.No. 5,755,683, so as to permit removal of any small air bubbles that mayotherwise tend to collect at the port. (The top port 49 of the deliverychamber 27 has a similar design, since air bubbles need to be removedfrom the delivery chamber as well.) The mixing chamber's top port 47 isdesigned to remove air from the mixing chamber, since air of coursetends to collect in the upper portion of the chamber. The bottom port 48is used to remove liquid from the mixing chamber 28, since liquid ofcourse tends to collect in the bottom portion of the mixing chamber.

[0041] As can be seen in FIGS. 5 and 6, which respectively show top andrear views of the back-plate component of the cassette, both thedelivery chamber 27 and the mixing chamber 28 have channels formed intothe rigid walls thereof. The channel 57 in the delivery chamber 27permits easier flow into, out of and through the delivery chamber 27when the membrane is resting against or near the rigid wall. As can beseen in FIG. 6, the upper portion 59 of the mixing chamber's channel isnarrower than the channel's lower portion 58. The channel's lowerportion 58 permits easier flow of liquid out of the mixing chamber 28when the membrane is resting against or near the chamber's rigid wall.The difference in groove depth promotes the flow of air and liquid fromthe top and bottom of the chamber respectively while minimizing thetotal volume contained in the groove.

[0042] Once the powdered drug is completely reconstituted, it may betreated by the system as a liquid drug, which may or may not be diluted.

[0043] After the drug has been thoroughly mixed by sloshing the liquidback and forth between the mixing chamber 28 and the vial 11 a, the drugis ready for delivery to the patient. If no further dilution of the drugis required, boluses of the drug are urged—by air pressure created bythe control unit against the mixing chamber's membrane, or negativepressure applied against the delivery chamber's membrane—from the mixingchamber 28 to the delivery chamber 27. From the delivery chamber, theseboluses of drug are delivered through valve 32 and stopcock valve 33 tothe patient in the same manner described above for delivering straightIV solution to the patient.

[0044] If dilution of the drug is required, smaller boluses of thereconstituted drug may be urged from the mixing chamber 28 to thedelivery chamber 27, into which additional IV solution may be introducedin the correct proportions from the IV solution source, in order tolower the concentration of the reconstituted drug. Once the drug in abolus is diluted to the desired level, the drug may be delivered to thepatient in the same manner described above. Each successive bolus isdiluted and delivered in this manner. The control unit tracks the volumeof drug delivered to the patient and the rate at which it wasadministered. Another method of diluting the drug is to introduce avolume of liquid from the IV fluid source into the mixing chamber to bemixed with the liquid drug.

[0045] If it is desired to supply to the patient only a fraction of thedrug in the vial, the unused portion of the reconstituted drug may bereturned to the vial 11 a.

[0046] When, after providing several boluses of reconstituted drug tothe delivery chamber 27, and the mixing chamber 28 is substantiallyemptied of the drug, any drug that may be in the manifold 45 or otherpassageway may be urged to the delivery chamber 27 by drawing air intothe manifold from the vent 24, so that substantially all of the drug maybe delivered to the patient before the next delivery cycle begins. Inorder to draw air in through the manifold 45, the air-vent valve 31 g isopened and the delivery-chamber inlet valve 31 b is opened, while allthe other valves 31 a, 31 c-31 f, 31 h-31 i, 32 are closed. The controlunit applies a negative pressure to the membrane of the delivery chamber27, so as to draw fluid through the manifold 45 into the deliverychamber. Air is thus drawn through the vent 24 to fill in after the drugbeing pulled through the manifold 45 into the delivery chamber 27. Inthe two-chambered system, air is also preferably drawn through themixing chamber 28, in order to remove remants of the drug from themixing chamber.

[0047] There are stages in the delivery cycle during which if air hasbeen drawn into the delivery chamber 27, it is important to remove theair from the chamber 27 without removing any of the drug. (The acousticvolume measurement system, which is the preferred method used to measurethe amount of liquid in the delivery chamber, does not work well ifthere is any bubble in the liquid.) To accomplish the removal of the airwithout permitting more than a tiny amount of reconstituted drug toescape, the delivery chamber is pressurized a little (with respect tothe manifold) and valve 31 b is opened and closed quickly; the chamber27 is again checked for the presence of a bubble. These steps arerepeated until no more air is detected. By keeping the pressuredifferential across the valve 31 b relatively small and opening thevalve for only a very short period of time, only a tiny amount, if any,of reconstituted drug can escape from the delivery chamber 27. If thevalve is allowed to be only partially opened during this process, evenless reconstituted drug can escape. Alternatively, the air may be pushedinto the relatively small manifold volume to control how much isreleased.

[0048] Before beginning a new delivery cycle, it may be desirable toclean any small amounts of the first drug from the passageways 25 sothat the two drugs do not mix. This cleansing of the cassette'spassageways may be accomplished by drawing IV solution from the IVsolution source and passing the IV solution into and out of the deliverychamber 27 (where the amount of IV solution may be measured), throughthe manifold 45 and through the mixing chamber 28. The emptied vial mayalso be rinsed. A sufficient amount of IV solution should be introducedinto the cassette 17 at this point in order to dilute to a safe,negligible concentration whatever remnants of the drug remain in thecassette so that the IV solution used to cleanse the cassette may besent to the patient. The amount of IV solution used should be enough toensure that the cassette is properly rinsed so that residue of the priordrug does not interact with the next drug.

[0049] It may be desired to deliver to the patient additional straightIV solution before delivering the next drug from vial 11 b. When it istime to prepare and deliver the drug from vial 11 b, the drug isprepared and delivered in the same manner as described above inconnection with preparing and delivering the drug from vial 11 a. Afterthe drug from vial 11 b has been prepared and delivered to the patient,and after the cassette is cleansed of any remnants of the drug from vial11 b, the drug from vial 11 c may in turn be prepared and delivered tothe patient.

[0050] Depending on the desired treatment, the liquid drug provided tothe cassette through port 26 may be provided to the patient before,between or after the delivery of the drugs in the vials 11 a-11 c. Theliquid drug provided through port 26 of course does not have toreconstituted; it may however need to be diluted prior to delivery.

[0051] The above-described system may be used in a variety of ways. Forinstance, the vials may be accessed in different orders (for example,vial 11 b, then 11 c and then 11 a, or first vial 11 c, then 11 a andthen 11 b). A vial may contain a powdered drug, which may bereconstituted, then diluted and then delivered, or which may simply bereconstituted and delivered. A vial may also contain a liquid drug,which may likewise be diluted and delivered, or simply be deliveredstraight. A drug may also be provided through the luer port 26 to bediluted and delivered, or simply delivered. The luer port 26 may alsoprovide a second IV fluid for use in reconstitution and/or dilution.Providing a secondary IV fluid through luer port 26, as well as aprimary IV fluid through port 22, is an important feature if the vialsattached to the cassette contain drugs that require different types offluids to be reconstituted and/or diluted properly.

[0052] When the cassette 17 is removed from the control unit 15, thecontrol unit is no longer able to control the membrane-based valves 31a-31 i, 32 and the stopcock valve 33. Each membrane-based valve assumesan open position if not being actuated by the control unit, and thestopcock valve 33 remains in an open position, if it had been in an openposition when the cassette was removed from the control unit. Withoutthe outlet free-flow-prevention valve 35 shown in FIGS. 2 and 3,concentrated drug could be accidentally delivered at an excessively highflow rate to the patient. Without the inlet free-flow-prevention valve34 shown in FIGS. 2 and 3, concentrated drug may make its way out of theinlet port 22 to the IV solution source 13, thereby contaminating the IVsolution source so that it cannot be safely used again. In addition,multiple drugs in the cassette and/or vial can mix creating hazardousand uncontrolled solutions.

[0053] The inlet and outlet free-flow-prevention valves 34 and 35 areacted on by actuators mounted in the control unit's door when thecassette 17 is removed from the control unit 15. When the door isopened, these actuators push the membranes of the free-flow-preventionvalves 34 and 35 into a closed position, and the membranes are shaped toremain in a closed position permanently once they are actuated. Thus,the removal of the cassette from the control unit closes the twofree-flow-prevention valves 34 and 35 and prevents liquid from flowingfrom the cassette to either the patient or the IV solution source.

[0054] FIGS. 7-10 show several views of a membrane used in a preferredembodiment of the free-flow-prevention valves 34 and 35 shown in FIGS. 2and 3. The membrane includes a central plug portion 72, a rib 76 formounting the membrane in the rigid cassette body, and a relatively thin,folded portion 74 that connects the plug portion 72 and the rib 76. Whenthe actuator pushes the exterior end 82 of the plug portion 72, theinterior end 83 of the plug portion is urged into the fluid passageway(which leads to either the cassette's IV solution inlet 22 or thecassette's liquid outlet 23). The folded portion 74 is folded further bythis action, such that the plug portion 72 is held in the closedposition blocking the fluid passageway.

[0055] Thus, removal of the cassette 17 from the control unit 15 causesthe free-flow-prevention valves 34, 35 to be closed in such a way thatthey cannot be easily opened, so that they are essentially permanentlyclosed. Thus, the cassette can no longer be used. If the cassette isre-inserted into the control unit, the control unit senses an occlusionupstream when it attempts to draw IV solution from the IV solutionsource, or it senses an occlusion downstream when it tries to deliverliquid to the patient. The control unit, in a preferred embodiment,sounds an alarm after several attempts are made to pump liquid into orout of the cassette. In an alternative embodiment, the cassette may beprovided, in addition to the free-flow-prevention valves, with abreak-away tab that is broken off by an actuator when the cassette isremoved from the control unit. When a cassette of this type is insertedinto the control unit, the control unit determines whether thebreak-away tab is present on the cassette. If such a tab is present, thecontrol unit proceeds as normal, checking for occlusions, etc. If thetab is missing, the control unit sounds an alarm indicating that thecassette has been used already, and a new cassette should be inserted.The break-away tab thus allows the control unit to avoid performingseveral occlusion checks if the cassette has already been used.

[0056] The control unit may also be programmed to sound alarms whenother potentially dangerous situations occur, and the control unitpreferably includes a keypad so that information regarding the desireddrug delivery cycles for a given patient may be entered into the systemso that the drugs may be prepared and delivered according the desiredcycles. Information regarding the patient may also be entered into orread by the control unit, as well as information regarding the medicalprovider who is entering the information. Information regarding theproper, safe dosage levels for various drugs may be programmed into thecontrol unit, so that if, for example, the medical provider attempts toenter a dosage level that is greater than what is normally permitted,the control unit sounds an alarm. The control unit may also beprogrammed to prevent the delivery of an unsafe dosage, or it may beprogrammed so that a medical provider with sufficient authority mayoverride the programmed maximum dosage levels.

[0057] In a preferred embodiment, the control unit is connected to ahospital-wide network, so that information in the control unit may beupdated easily. For instance, information regarding the patient, such asweight and drug allergies, may be entered into the hospital network atadmissions. When the patient is to be connected to thedrug-preparation-and-delivery system described hereinabove, thepatient's identification code may be entered into or read by the controlunit, and the control unit can then access the network so that thepatient's information is available to permit the control unit to soundan alarm if the patient's drug allergies or low weight could create adangerous situation based on the drugs that are to be delivered or drugdelivery cycles that are to be implemented. A list of dangerous druginteractions may be kept and updated by the pharmacy as well. All drugsprovided to the patient, including the drugs administered by thedrug-preparation-and-delivery system described hereinabove, as well asdrugs provided by traditional means, may be recorded in the hospitalnetwork, and the control unit may sound an alarm is a dangerousinteraction may occur. Likewise, proper dosage and delivery-cycleinformation may be kept and updated by the hospital's pharmacy, so as toprovide the framework for safe drug delivery. If the desired drugdelivery cycle entered into the control unit does not fall within thesafety framework, the control unit may sound an alarm.

[0058] The control unit may also store information regarding the drugsdelivered to the patient and the time frames of the deliveries. Thisinformation may be downloaded into the network, so that it is availablefor later review by a medical provider, and so that the patient (or thepatient's insurance company) may be properly billed for the drugs thatare actually delivered to the patient.

[0059] Although the invention has been described with reference toseveral preferred embodiments, it will be understood by one of ordinaryskill in the art that various modifications can be made withoutdeparting from the spirit and the scope of the invention, as set forthin the claims hereinbelow.

What is claimed is:
 1. A system for controlling flow through anintravenous line, the system comprising: a disposable cassette having: afirst valve chamber defined by a first rigid wall and a first flexiblemembrane, and a second valve chamber defined by a second rigid wall anda second flexible membrane; and a control unit having a cam, a firstactuator disposed adjacent the first flexible membrane so that movementof the first actuator causes a change in pressure on the first flexiblemembrane, and a second actuator disposed adjacent the second flexiblemembrane so that movement of the second actuator causes a change inpressure on the second flexible membrane, wherein the cam and actuatorsare disposed with respect to each other such that, as the cam isrotated, the actuators are moved.
 2. The system of claim 1 wherein thecam is shaped so that, at any time, at least one actuator is urging thecorresponding flexible membrane into a closed position.
 3. The system ofclaim 2 wherein the cassette further includes a pressure-conductionchamber located in a fluid passageway between the first and second valvechambers.